Jie Li, Wenshan Nan, Xiaoli Huang, Huali Meng, Shue Wang, Yan Zheng, Ying Li, Hui Li, Zhiyue Zhang, Lei Du, Xiao Yin, Hao Wu
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引用次数: 0
Abstract
Diabetic cardiomyopathy (DC) leads to heart failure, with few effective approaches for its intervention. Eicosapentaenoic acid (EPA) is an essential nutrient that benefits the cardiovascular system, but its effect on DC remains unknown. Here, we report that EPA protects against DC in streptozotocin and high-fat diet-induced diabetic mice, with an emphasis on the reduction of cardiac M1-polarized macrophages. In vitro, EPA abrogates cardiomyocyte injury induced by M1-polarized macrophages, switching macrophage phenotype from M1 to Mox, but not M2, polarization. Moreover, macrophage Mox polarization combats M1-polarized macrophage-induced cardiomyocyte injury. Further, heme oxygenase 1 (HO-1) was identified to maintain the Mox phenotype, mediating EPA suppression of macrophage M1 polarization and the consequential cardiomyocyte injury. Mechanistic studies reveal that G-protein-coupled receptor 120 mediates the upregulation of HO-1 by EPA. Notably, EPA promotes Mox polarization in monocyte-derived macrophages from diabetic patients. The current study provides EPA and macrophage Mox polarization as novel strategies for DC intervention.
期刊介绍:
EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings.
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